Carbon availability affects nitrogen source utilisation by Hymenoscyphus ericae

We compared the ability of five strains of the ericoid mycorrhizal fungus Hymenoscyphus ericae to utilise glutamine, ammonium or nitrate at high or low carbon (C) availability. The pattern of intraspecific variation in growth was affected by C availability. When C supply was high, growth differences between strains were explained by the total amount of nitrogen (N) taken up, suggesting variation in uptake kinetics. Under C-limiting conditions, strain differences were linked with their nitrogen use efficiency, implying intraspecific differences in N metabolism. The relationship between growth on glutamine and pH shifts in the media indicated that there was intraspecific variation in glutamine transporters. In addition, the correlation between pH changes and the amount of glutamine-N recovered as ammonium in the media indicated that there were intraspecific variations within the enzymatic pathways involved in glutamine metabolism. Our findings, compared with those of a previous study involving the same ericoid strains, draw attention to the temporal variation in nitrogen source utilisation by ericoid mycorrhizal fungi when maintained in axenic culture.

The mechanistic basis of interactions between mycorrhizal associations and toxic metal cations

Mycorrhizal associations, including ericoid, arbuscular and ecto-mycorrhizas, are found colonising highly metal contaminated soils. How do mycorrhizal fungi achieve metal resistance, and does this metal resistance confer enhanced metal resistance to plant symbionts? These are the questions explored in this review by considering the mechanistic basis of mycorrhizal adaptation to metal cations. Recent molecular and physiological studies are discussed. The review reappraises what constitutes metal resistance in the context of mycorrhizal associations and sets out the constitutive and adaptive mechanisms available for mycorrhizas to adapt to contaminated sites. The only direct evidence of mycorrhizal adaptation to metal cation pollutants is the exudation of organic acids to alter pollutant availability in the rhizosphere. This is not to say that other mechanism of adaptation do not exist, but conclusive evidence of adaptive mechanisms of tolerance are lacking. For constitutive mechanisms of resistance, there is much more evidence, and mycorrhizas possess the same constitutive mechanisms for dealing with metal contaminants as other organisms. Rhizosphere chemistry is critical to understanding the interactions of mycorrhizas with polluted soils. Soil pH, mineral weathering, pollutant precipitation with plant excreted organic acids all may have a key role in constitutive and adaptive tolerance of mycorrhizal associations present on contaminated sites. The responses of mycorrhizal fungi to toxic metal cations are diverse. This, linked to the fact that mycorrhizal diversity is normally high, even on highly contaminated sites, suggests that this diversity may have a significant role in colonisation of contaminated sites by mycorrhizas. That is, the environment selects for the fungal community that can best cope with the environment, so having diverse physiological attributes will enable colonisation of a wide range of metal contaminated micro-habitats.

HIGH SPEED CMOS/SOS IMPLEMENTATION OF A BIT LEVEL SYSTOLIC CORRELATOR.

The fabrication and performance of the first bit-level systolic correlator array is described. The application of systolic array concepts at the bit level provides a simple and extremely powerful method for implementing high-performance digital processing functions. The resulting structure is highly regular, facilitating yield enhancement through fault-tolerant redundancy techniques and therefore ideally suited to implementation as a VLSI chip. The CMOS/SOS chip operates at 35 MHz, is fully cascadable and exhibits 64-stage correlation for 1-bit reference and 4-bit data. 7 refs.

Lung Microbiota and Bacterial Abundance in Patients with Bronchiectasis when Clinically Stable and during Exacerbation

RATIONALE: Characterization of bacterial populations in infectious respiratory diseases will provide improved understanding of the relationship between the lung microbiota, disease pathogenesis and treatment outcomes.

OBJECTIVES: To comprehensively define lung microbiota composition during stable disease and exacerbation in bronchiectasis patients.

METHODS: Sputum was collected from patients when clinically stable and before and after completion of antibiotic treatment of exacerbations. Bacterial abundance and community composition were analyzed using anaerobic culture and 16S rDNA pyrosequencing.

MEASUREMENTS AND MAIN RESULTS: In clinically stable patients, aerobic and anaerobic bacteria were detected in 40/40 (100%) and 33/40 (83%) sputum samples, respectively. The dominant organisms cultured were P. aeruginosa (n=10 patients), H. influenzae (n=12), Prevotella (n=18) and Veillonella (n=13). Pyrosequencing generated over 150,000 sequences, representing 113 distinct microbial taxa; the majority of observed community richness resulted from taxa present in low abundance with similar patterns of phyla distribution in clinically stable patients and patients at the onset of exacerbation. Following treatment of exacerbation, there was no change in total (p=0.925), aerobic (p=0.917) or anaerobic (p=0.683) load and only a limited shift in community composition. Agreement for detection of bacteria by culture and pyrosequencing was good for aerobic bacteria such as P. aeruginosa (kappa=0.84) but poorer for other genera including anaerobes. Lack of agreement was largely due to bacteria been detected by pyrosequencing but not by culture.

CONCLUSIONS: A complex microbiota is present in the lungs of bronchiectasis patients which remains stable through treatment of exacerbations suggesting that changes in microbiota composition do not account for exacerbations.

Therapeutic Effects of Human Mesenchymal Stem Cells in Ex Vivo Human Lungs Injured with Live Bacteria

Rationale: Mesenchymal stem cells secrete paracrine factors that can regulate lung permeability and decrease inflammation, making it a potentially attractive therapy for acute lung injury. However, concerns exist whether mesenchymal stem cells' immunomodulatory properties may have detrimental effects if targeted toward infectious causes of lung injury. Objectives: Therefore, we tested the effect of mesenchymal stem cells on lung fluid balance, acute inflammation, and bacterial clearance. Methods: We developed an Escherichia coli pneumonia model in our ex vivo perfused human lung to test the therapeutic effects of mesenchymal stem cells on bacterial-induced acute lung injury. Measurements and Main Results: Clinical-grade human mesenchymal stem cells restored alveolar fluid clearance to a normal level, decreased inflammation, and were associated with increased bacterial killing and reduced bacteremia, in part through increased alveolar macrophage phagocytosis and secretion of antimicrobial factors. Keratinocyte growth factor, a soluble factor secreted by mesenchymal stem cells, duplicated most of the antimicrobial effects. In subsequent in vitro studies, we discovered that human monocytes expressed the keratinocyte growth factor receptor, and that keratinocyte growth factor decreased apoptosis of human monocytes through AKT phosphorylation, an effect that increased bacterial clearance. Inhibition of keratinocyte growth factor by a neutralizing antibody reduced the antimicrobial effects of mesenchymal stem cells in the ex vivo perfused human lung and monocytes grown in vitro injured with E. coli bacteria. Conclusions: In E. coli-injured human lungs, mesenchymal stem cells restored alveolar fluid clearance, reduced inflammation, and exerted antimicrobial activity, in part through keratinocyte growth factor secretion.

Relative Respiratory Syncytial Virus Cytopathogenesis in Upper and Lower Respiratory Tract Epithelium

Respiratory syncytial virus (RSV) is a major pathogen that primarily infects airway epithelium. Most infants suffer mild upper respiratory tract (URT) symptoms, while approximately one third progress to lower respiratory tract (LRT) involvement. Despite the ubiquity of URT infection, little is known about the relative cytopathogenesis of RSV infection in infant URT and LRT.

Cheetahs, Acinonyx jubatus, balance turn capacity with pace when chasing prey

Predator–prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world's fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s-1 and accelerated up to 7.5 m s-2 with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5–8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival.

Food miles or carbon emissions? Exploring labeling preference for food transport footprint with a stated choice study

The ecological footprint of food transport can be communicated using carbon dioxide emissions (CO2 label) or by providing information about both the length of time and the mileage travelled (food miles label). We use stated choice data to estimate conventional unobserved taste heterogeneity models and extend them to a specification that also addresses attribute nonattendance. The implied posterior distributions of the marginal willingness to pay values are compared graphically and are used in validation regressions. We find strong bimodality of taste distribution as the emerging feature, with different groups of subjects having low and high valuations for these labels. The best fitting model shows that CO2 and food miles valuations are much correlated. CO2 valuations can be high even for those respondents expressing low valuations for food miles. However, the reverse is not true. Taken together, the results suggest that consumers tend to value the CO2 label at least as much and sometimes more than the food miles label.

Influence of concrete composition on anchorage bond behavior of prestressing reinforcement

An experimental research addressing the effects of concrete composition and strength on anchorage bond behavior of prestressing reinforcement is presented to clarify the effect of material properties that have appeared contradictory in previous literature. Bond stresses and anchorage lengths have been obtained in twelve concrete mixes made up of different cement contents (C) – 350 to 500 kg/m3 – and water/cement (w/c) ratios – 0.3 to 0.5 – with compressive strength at 24 h ranging from 24 to 55 MPa. A testing technique based on measuring the prestressing force in specimens with different embedment lengths has been used. The results show that anchorage length increases when w/c increases, more significantly when C is higher; the effect of C reveals different trends based on w/c. The obtained anchorage bond stresses are greater for higher concrete compressive strength, and their average ratio of 1.45 with respect to transmission bond stresses implies a potential bond capacity.

How Outcomes Are Defined in Clinical Trials of Mechanically Ventilated Adults and Children

Systematic reviews have considerable potential to provide evidence-based data to aid clinical decision-making. However, there is growing recognition that trials involving mechanical ventilation lack consistency in the definition and measurement of ventilation outcomes, creating difficulties in combining data for meta-analyses. To address the inconsistency in outcome definitions, international standards for trial registration and clinical trial protocols published recommendations, effectively setting the “gold standard” for reporting trial outcomes. In this Critical Care Perspective, we review the problems resulting from inconsistent outcome definitions and inconsistent reporting of outcomes (outcome sets). We present data highlighting the variability of the most commonly reported ventilation outcome definitions. Ventilation outcomes reported in trials over the last 6 years typically fall into four domains: measures of ventilator dependence; adverse outcomes; mortality; and resource use. We highlight the need, first, for agreement on outcome definitions and, second, for a minimum core outcome set for trials involving mechanical ventilation. A minimum core outcome set would not restrict trialists from measuring additional outcomes, but would overcome problems of variability in outcome selection, measurement, and reporting, thereby enhancing comparisons across trials.

Lung Clearance Index Is a Repeatable and Sensitive Indicator of Radiological Changes in Bronchiectasis

RATIONALE: In bronchiectasis there is a need for improved markers of lung function to determine disease severity and response to therapy.

OBJECTIVES: To assess whether the lung clearance index is a repeatable and more sensitive indicator of computed tomography (CT) scan abnormalities than spirometry in bronchiectasis.

METHODS: Thirty patients with stable bronchiectasis were recruited and lung clearance index, spirometry, and health-related quality of life measures were assessed on two occasions, 2 weeks apart when stable (study 1). A separate group of 60 patients with stable bronchiectasis was studied on a single visit with the same measurements and a CT scan (study 2).

MEASUREMENTS AND MAIN RESULTS: In study 1, the intervisit intraclass correlation coefficient for the lung clearance index was 0.94 (95% confidence interval, 0.89 to 0.97; P < 0.001). In study 2, the mean age was 62 (10) years, FEV1 76.5% predicted (18.9), lung clearance index 9.1 (2.0), and total CT score 14.1 (10.2)%. The lung clearance index was abnormal in 53 of 60 patients (88%) and FEV1 was abnormal in 37 of 60 patients (62%). FEV1 negatively correlated with the lung clearance index (r = -0.51, P < 0.0001). Across CT scores, there was a relationship with the lung clearance index, with little evidence of an effect of FEV1. There were no significant associations between the lung clearance index or FEV1 and health-related quality of life.

CONCLUSIONS: The lung clearance index is repeatable and a more sensitive measure than FEV1 in the detection of abnormalities demonstrated on CT scan. The lung clearance index has the potential to be a useful clinical and research tool in patients with bronchiectasis.

Statin Use and Risk of Delirium in the Critically Ill

Rationale: Delirium is common in intensive care unit (ICU) patients and is a predictor of worse outcomes and neuroinflammation is a possible mechanism. The antiinflammatory actions of statins may reduce delirium.

Objectives: To determine whether critically ill patients receiving statin therapy had a reduced risk of delirium than those not on statins.

Methods: A prospective cohort analysis of data from consecutive ICU patients admitted to a UK mixed medical and surgical critical care unit between August 2011 and February 2012; the Confusion Assessment Method for ICU was used to determine the days each patient was assessed as being free of delirium during ICU admission.

Measurements and Main Results: Delirium-free days, daily administration of statins, and serum C-reactive protein (CRP) were recorded. Four hundred and seventy consecutive critical care patients were followed, of whom 151 patients received statins. Using randomeffects multivariable logistic regression, statin administration the previous evening was associated with the patient being assessed as free of delirium (odds ratio, 2.28; confidence interval, 1.01-5.13; P , 0.05) and with lower CRP (b = 20.52; P , 0.01) the following day. When the association between statin and being assessed as free of delirium was controlled for CRP, the effect size became nonsignificant (odds ratio, 1.56; confidence interval, 0.64-3.79; P = 0.32).

Conclusions: Ongoing statin therapy is associated with a lower daily risk of delirium in critically ill patients. An ongoing clinical trial, informed by this study, is investigating if statins are a potential therapy for delirium in the critically ill.Copyright © 2014 by the American Thoracic Society.

The Beta Agonist Lung Injury Trial Prevention:A Randomized Controlled Trial

Rationale: Experimental studies suggest that pretreatment with b-agonists might prevent acute lung injury (ALI).

Objectives: To determine if in adult patients undergoing elective esophagectomy, perioperative treatment with inhaled b-agonists effects the development of early ALI.

Methods:We conducted a randomized placebo-controlled trial in 12 UK centers (2008-2011). Adult patients undergoing elective esophagectomy were allocated to prerandomized, sequentially numbered treatment packs containing inhaled salmeterol (100 mg twice daily) or a matching placebo. Patients, clinicians, and researchers were masked to treatment allocation. The primary outcome was development of ALI within 72 hours of surgery. Secondary outcomes were ALI within 28 days, organ failure, adverse events, survival, and health-related quality of life. An exploratory substudy measured biomarkers of alveolar-capillary inflammation and injury.

Measurements and Main Results: A total of 179 patients were randomized to salmeterol and 183 to placebo. Baseline characteristics were similar. Treatment with salmeterol did not prevent early lung injury (32 [19.2%] of 168 vs. 27 [16.0%] of 170; odds ratio [OR], 1.25; 95% confidence interval [CI], 0.71-2.22). There was no difference in organ failure, survival, or health-related quality of life.Adverse events were less frequent in the salmeterol group (55 vs. 70; OR, 0.63; 95% CI, 0.39-0.99), predominantly because of a lower number of pneumonia (7 vs. 17; OR, 0.39; 95% CI, 0.16-0.96). Salmeterol reduced some biomarkers of alveolar inflammation and epithelial injury.

Conclusion: Perioperative treatment with inhaled salmeterol was well tolerated but did not prevent ALI.

Clinical trial registered with International Standard Randomized Controlled Trial Register (ISRCTN47481946) and European Union database of randomized Controlled Trials (EudraCT 2007-004096-19).Copyright © 2014 by the American Thoracic Society.